Genetic factors contributed by both host and virus interact to determine the effects of murine leukemia virus (MuLV) infection of mice. Host genes which influence MuLV-related hematopoietic system disease have been identified and chromosomally mapped; these include MuLV ecotropic virus induction loci, which represent integrated proviral sequences, and genes controlling infection and spread of virus, such as Fv-1, determining sensitivity to infection by N- or B-tropic MuLVs, and Rmcf, which affects replication and generation of MCF viruses. In order to study gene effects isolated from other host genetic differences, a number of strains of NFS mice congenic for different virus induction loci (v-congenics) and for the MCF MuLV resistance allele Rmcfr have been established. Profiles of spontaneous disease have been established for the v-congenics and those with high ecotropic MuLV expression are used in pathogenicity assays of MCF viruses, which may require helper virus to express oncogenic activity. Their use has led to the isolation of 2 new ras-containing acute transforming viruses and an unusual variant of LP-BM5 MCF virus has been revealed. Studies of host factors influencing MuLV related disease utilize NFS-Rmcfr congenics for analysis of LTR-region recombinants of Moloney and Friend MuLV, and a variety of inbred strains are used for investigation of the strain distribution of sensitivity to LP-BM5 disease. In the latter case, host genes which are known to affect MuLV spread appear to have reduced activity on certain genetic backgrounds.